MedicalResearch.com Interview with:
Prof. h.c.* Dr. Farid Saad
on behalf of Dr. Haider and co-authors
Global Medical Affairs, Andrology
c/o Bayer Pharma AG, D-13342 Berlin
*Gulf Medical University, Ajman, UAE
Medical Research: What is the background for this study?
Response: In early 1940s Dr. Charles Huggins demonstrated that in few men with metastatic prostate cancer, castration reduced tumor growth and androgen administration promoted tumor growth. This observation became the corner stone of androgen deprivation therapy (ADT) in men with prostate cancer for the past 7 decades without any clinical evidence to the contrary.
Indeed, normal prostate growth depends on androgens and therefore testosterone and its metabolite DHT are responsible for the biochemical signaling in the prostate cells through interaction with the androgen receptor. Since tumor cells have been transformed from normal epithelial cells, it is no surprise that they retained the expression of the androgen receptor and continue to depend on their growth on the androgen signal. For the past 7 decades, physicians thought that testosterone is a carcinogen for the prostate, despite lack of any biochemical or clinical data. This long period of training physicians on this unproven concept, has precipitated in the minds of many clinicians that testosterone (T) causes prostate cancer. Based on a plethora of clinical data, there is no evidence to support such myth. In fact, many recent studies have debunked this hypothesis based on longitudinal and prospective studies.
A newly advanced hypothesis was formulated suggesting that “T therapy does not pose a greater risk for development of PCa.” However this hypothesis is met with considerable skepticism. Interestingly, however, no new compelling evidence is available to discredit or dismiss this newly advanced hypothesis.
Medical Research: What are the main findings?
Response: The main finding of our studies are the incidence of prostate cancer from three large independent observational cohorts, in which more than 1,000 hypogonadal men were treated with T therapy for up to 17 years, no significant increase in the incidence of prostate cancer (<2%) was found.
In fact, the incidence of prostate cancer in the testosterone treated men was far less than that detected in general screening trials. In a large screening trial in the U.S., in which 38,345 men age 55 to 74 years in the control arm were followed for 7 years, 7.35% were diagnosed with prostate cancer. Similarly, data from an European study in which 72,891 patients, age 50 to 74 years and followed up for 11 years showed that 9.6% of men were diagnosed with prostate cancer,
Our findings suggest that the incidence of prostate cancer in patients on T therapy was not greater than in the general population. To date, there is no convincing evidence that T therapy is a risk factor for PCa. Thus, fear that T therapy causes PCa may not be justified in light of the aforementioned arguments.
Medical Research: What should clinicians and patients take away from your report?
Response: Although definitive safety data regarding testosterone therapy must await large, long-term, controlled trials, our data suggest that testosterone therapy does not increase the risk of prostate cancer. Clinicians and patients need to appreciate that in the absence of prostate cancer and in patients with history of prostate cancer which were treated and are free of the disease, testosterone therapy of hypogonadism is warranted, with appropriate and close monitoring. The risk of prostate cancer in hypogonadal men receiving testosterone therapy seems lower than in the general population. Careful evaluations and monitoring is necessary.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: We believe that clinical trials which are well designed and controlled, with a large number of patients and for a reasonable long period of time is important to finally solidify the evidence that testosterone does not represent a risk of prostate cancer. Unfortunately, these studies are costly and no government agency or industry is willing to invest the enormous amount of resources needed to answer this very critical question. Nevertheless, as we move along, all types of studies, irrespective of its nature will produce evidence which will either support or dismiss the notion that use of testosterone is safe in hypogonadal men.
Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy: Observations from 5-Year Median Followup of 3 Registries
Haider A, Zitzmann M, Doros G, Isbarn H, Hammerer P, Yassin A
J Urol. 2014 Jun 26. pii: S0022-5347(14)03885-3. doi: 10.1016/j.juro.2014.06.071.
[Epub ahead of print]